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Moon Hee Lee,1 Seok-Kyu Yoon,1 Hyungsub Kim,2 Yong-Soon Cho,3 Sungpil Han,4 Shi Hyang Lee,1 Kyun-Seop Bae,1 Jina Jung,5 Sung Hee Hong,5 Hyeong-Seok Lim1 1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea; 2Department of Emergency Medical Services, College of Health Sciences, Eulji University, Seongnam, Republic of Korea; 3Department of Pharmacology and Clinical Pharmacology, Inje University College of Medicine, Busan, Republic of Korea; 4Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 5Hanmi Pharmaceutical Co. Ltd., Seoul, Republic of KoreaCorrespondence: Hyeong-Seok Lim, Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-2-3010-4613, Fax +82-2-3010-4623, Email mdlhs@amc.seoul.krPurpose: The combined administration of bazedoxifene, a tissue-selective estrogen receptor modulator, and cholecalciferol can be a promising therapeutic option for postmenopausal osteoporosis patients. This study aimed to examine the pharmacokinetic interactions between these two drugs and the tolerability of their combined administration in healthy male subjects.Patients and Methods: Thirty male volunteers were randomly assigned to one of the six sequences comprised of three treatments: bazedoxifene 20 mg monotherapy, cholecalciferol 1600 IU monotherapy, and combined bazedoxifene and cholecalciferol therapy. For each treatment, a single dose of the investigational drug(s) was administered orally, and serial blood samples were collected to measure the plasma concentrations of bazedoxifene and cholecalciferol. Pharmacokinetic parameters were calculated using the non-compartmental method. The point estimate and 90% confidence interval (CI) of the geometric mean ratio (GMR) were obtained to compare the exposures of combined therapy and monotherapy. The pharmacokinetic parameters compared were the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast). The safety and tolerability of the combined therapy were assessed in terms of the frequency and severity of adverse events (AEs).Results: For bazedoxifene, the GMR (90% CI) of the combined therapy to monotherapy was 1.044 (0.9263– 1.1765) for Cmax and 1.1329 (1.0232– 1.2544) for AUClast. For baseline-adjusted cholecalciferol, the GMR (90% CI) of the combined therapy to monotherapy was 0.8543 (0.8005– 0.9117) for Cmax and 0.8056 (0.7445– 0.8717) for AUClast. The frequency of AEs observed was not significantly different between the combined therapy and monotherapy, and their severity was mild in all cases.Conclusion: A mild degree of pharmacokinetic interaction was observed when bazedoxifene and cholecalciferol were administered concomitantly to healthy male volunteers. This combined therapy was well tolerated at the dose levels used in the present study.Keywords: bazedoxifene, cholecalciferol, drug-drug interaction, pharmacokinetics, tolerability

This paper presents an all-in-one encoder/decoder approach for the nondestructive identification of three-dimensional (3D)-printed objects. The proposed method consists of three parts: 3D code insertion, terahertz (THz)-based detection, and code extraction. During code insertion, a relevant one-dimensional (1D) identification code is generated to identify the 3D-printed object. A 3D barcode corresponding to the identification barcode is then generated and inserted into a blank bottom area inside the object's stereolithography (STL) file. For this objective, it is necessary to find an appropriate area of the STL file and to merge the 3D barcode and the model within the STL file. Next the information generated inside the object is extracted by using THz waves that are transmitted and reflected by the output 3D object. Finally, the resulting THz signal from the target object is detected and analyzed to extract the identification information. We implemented and tested the proposed method using a 3D graphic environment and a THz time-domain spectroscopy system. The experimental results indicate that one-dimensional barcodes are useful for identifying 3D-printed objects because they are simple and practical to process. Furthermore, information efficiency can be increased by using an integral fast Fourier transform to identify any code located in areas deeper within the object. As 3D printing is used in various fields, the proposed method is expected to contribute to the acceleration of the distribution of 3D printing empowered by the integration of the internal code insertion and recognition process.

The diversity of health contexts in which members of the US Latinx population establish residence may provide insights into the variety of health challenges they face. We investigated differences in health professional shortages, general health services, health care safety-net supply, health access, and population health rankings across 3,113 US counties classified as established, new, or other Latinx population destinations. Compared with new destinations, established destinations had more health professional shortages, as well as higher rates of child and adult health uninsurance. New destinations had fewer health care safety-net services per 100,000 county residents than established destinations. Health contexts thus differ in significant ways across new and established Latinx destinations, and these differences have key implications for Latinx immigrant health.

Kudoa septempunctata is a myxosporean parasite that infects the trunk muscles of olive flounder (Paralichthys olivaceus) and has been reported to cause foodborne illnesses in humans. However, the molecular mechanisms underlying K. septempunctata spore toxicity remain largely unknown. In this study, the gastroenteropathy of K. septempunctata was examined in human colon adenocarcinoma cells as well as experimental mice inoculated with spores. We found that K. septempunctata decreased transepithelial resistance and disrupted epithelial tight junctions by deleting ZO-1 in Caco-2 monolayers. Additionally, serotonin (5-HT), an emetic neurotransmitter, was increased in K. septempunctata-inoculated cells. In vivo, K. septempunctata spores induced diarrhea in suckling mice (80% in ddY and 70% in ICR mice), with a minimum provocative dose of 2 × 105 K. septempunctata spores. In house musk shrews, K. septempunctata induced emesis within 1 h and induced serotonin secretion in the intestinal epithelium. In conclusion, K. septempunctata may induce diarrhea and emesis by increasing intestinal permeability and serotonin secretion.

Peroxisome proliferator-activated receptor gamma (PPARɣ) agonists exert powerful anticancer effects by suppressing tumor growth. In this study, we developed PPZ023 (1-(2-(ethylthio)benzyl)-4-(2-methoxyphenyl)piperazine), a novel PPAR ligand candidate, and investigated the underlying signaling pathways in both non-small-cell lung cancer (NSCLC) and radio-resistant NSCLC cells. To identify whether PPZ023 has anticancer effects in NSCLC and radioresistant NSCLC cells, we performed WST-1, LDH, Western blot, and caspase-3 and -9 activity assays. Furthermore, we isolated exosomes from PPZ023-treated NSCLC cells and studied cell death signaling. PPZ023 reduces cell viability and increases LDH cytotoxicity and caspase-3 activity in NSCLC cells. PPZ023 induces cell death by generating reactive oxygen species (ROS) and triggering mitochondrial cytochrome c release. PPZ023 treatment causes cell death via the PERK–eIF2α–CHOP axis in both NSCLC cell lysates and exosomes, and PERK and CHOP knockdown significantly blocks ER stress-mediated apoptosis by reducing cleaved caspase-3. Interestingly, diphenyleneiodonium (DPI, a Nox inhibitor) inhibits PPZ023-induced cell death via ER stress, and PPARɣ knockdown inhibits PPZ023-induced ROS, ER stress, and cell death. Moreover, PPZ023, in combination with radiation, causes synergic cell death via exosomal ER stress in radioresistant NSCLC cells, indicating that PPZ023/radiation overcomes radioresistance. Taken together, our results suggest that PPZ023 is a powerful anticancer reagent for overcoming radioresistance., Cancer: Reversing resistance to radiotherapy A novel small molecule drug candidate known as PPZ023 could be a powerful anti-cancer agent due to its ability to overcome the resistance of tumors to radiation therapy. Sung Hee Hong and colleagues at the Korea Institute of Radiological and Medical Sciences in Seoul, South Korea, investigated the effects of the molecule on lung cancer cells, including cells that that had acquired resistance to radiotherapy. PPZ023 induces the death of cancer cells by binding to a protein in a known signaling pathway, which generates damaging chemicals known as reactive oxygen species. The researchers identified additional molecular details of the anti-cancer activity. They found the radiotherapy resistance of cancer cells is reversed when PPZ023 promotes cell death via a pathway interfering with the folding of newly formed proteins in a cell structure called the endoplasmic reticulum.

The study attempted to propose refined question items used for eight types of lectures practiced in college settings (i.e., theory-based learning, flipped learning, discussion-based lectures, problem-based learning, co-teaching, Capstone Design, e-learning, and laboratory lectures). Its purpose was to help students objectively and accurately evaluate the lectures so that the instructors could use the data to improve their teaching effectiveness and to heighten student satisfaction. Extracting data from 15 journal publishers, the study investigated 34 articles published since 2013 in relation to lecture evaluations. Results entail different lecture evaluation question items that well match distinct features each lecture type entails. Further implications for future studies are proposed based on the findings.

Objectives This study aims to examine the effect of adolescent suicide survivors' experience on suicide death risk, and the effect of referral to mental health services (hereafter referral) in this regard. Methods This study used the data of 878 suicide-deceased and suicide-attempted adolescents aged 8-19 years, managed by the Suicide and School Mental Health Institute from 2016 to 2018. Results Regression analysis for main effects showed that although suicide experience had no direct effect on suicide death, non-referral status was associated with a greater risk of death by suicide. While the "non-suicide survivor with non-referral" and "suicide survivor with non-referral" groups showed 1.87 [adjusted odds ratio=1.87, 95% confidence interval (CI)=1.21-2.89] and 4.59 (adjusted odds ratio= 4.59, 95% CI=2.02-10.42) times higher odds of suicide death, respectively, the "suicide survivor with referral" group showed no difference compared to the "non-suicide survivor with referral" group. Conclusion From these findings, there is a need to strengthen referral to mental health services and apply complicated grief treatment to improve the mental health of adolescent suicide survivors.

The protozoan parasiteToxoplasma gondii(T. gondii) causes one of the most common human zoonotic diseases and infects approximately one-third of the global population.T. gondiiinfects nearly every cell type and causes severe symptoms in susceptible populations. In previous laboratory animal studies,T. gondiimovement and transmission were not analyzed in real time. In a three-dimensional (3D) microfluidic assay, we successfully supported the complex lytic cycle ofT. gondiiin situ by generating a stable microvasculature. The physiology of theT. gondii-infected microvasculature was monitored in order to investigate the growth, paracellular and transcellular migration, and transmission ofT. gondii, as well as the efficacy ofT. gondiidrugs.

Pluripotent stem cell-derived cerebral organoids have the potential to recapitulate the pathophysiology of in vivo human brain tissue, constituting a valuable resource for modelling brain disorders, including infectious diseases. Toxoplasma gondii, an intracellular protozoan parasite, infects most warm-blooded animals, including humans, causing toxoplasmosis. In immunodeficient patients and pregnant women, infection often results in severe central nervous system disease and fetal miscarriage. However, understanding the molecular pathophysiology of the disease has been challenging due to limited in vitro model systems. Here, we developed a new in vitro model system of T. gondii infection using human brain organoids. We observed that tachyzoites can infect human cerebral organoids and are transformed to bradyzoites and replicate in parasitophorous vacuoles to form cysts, indicating that the T. gondii asexual life cycle is efficiently simulated in the brain organoids. Transcriptomic analysis of T. gondii-infected organoids revealed the activation of the type I interferon immune response against infection. In addition, in brain organoids, T. gondii exhibited a changed transcriptome related to protozoan invasion and replication. This study shows cerebral organoids as physiologically relevant in vitro model systems useful for advancing the understanding of T. gondii infections and host interactions.

The diversity of health contexts in which members of the US Latinx population establish residence may provide insights into the variety of health challenges they face. We investigated differences in health professional shortages, general health services, health care safety-net supply, health access, and population health rankings across 3,113 US counties classified as established, new, or other Latinx population destinations. Compared with new destinations, established destinations had more health professional shortages, as well as higher rates of child and adult health uninsurance. New destinations had fewer health care safety-net services per 100,000 county residents than established destinations. Health contexts thus differ in significant ways across new and established Latinx destinations, and these differences have key implications for Latinx immigrant health.

Among several anti-cancer therapies, chemotherapy can be used regardless of the stage of the disease. However, development of anti-cancer agents from potential chemicals must be executed very cautiously because of several problems, such as safety, drug resistance, and continuous administration. Most chemotherapeutics selectively cause cancer cells to undergo apoptosis. In this study, we tested the effects of a novel chemical, the benzothiazole derivative N-[2-[(3,5-dimethyl-1,2-oxazol-4-yl)methylsulfanyl]-1,3-benzothiazol-6-yl]-4-oxocyclohexane-1-carboxamide (PB11) on the human cell lines U87 (glioblastoma), and HeLa (cervix cancer). It was observed that this chemical was highly cytotoxic for these cells (IC50s < 50 nM). In addition, even 40 nM PB11 induced the classical apoptotic symptoms of DNA fragmentation and nuclear condensation. The increase of caspase-3 and -9 activities also indicated an increased rate of apoptosis, which was further confirmed via Western blotting analysis of apoptosis-associated proteins. Accordingly, PB11 treatment up-regulated the cellular levels of caspase-3 and cytochrome-c, whereas it down-regulated PI3K and AKT. These results suggest that PB11 induces cytotoxicity and apoptosis in cancer cells by suppressing the PI3K/AKT signaling pathways and, thus, may serve as an anti-cancer therapeutic.

Objectives Our study aimed to analyze the demographic and clinical characteristics of children and adolescents during their first visit to psychiatric outpatient departments for the management of suicidal ideation and behavior, and to compare the changes before and in 2012 or later. Methods This multicenter study was conducted at five university hospitals in a metropolitan area in South Korea. Medical records of patients aged 6-18 years were retrospectively reviewed from January 2009 to December 2016. Patients were analyzed by classifying them into suicidal and non-suicidal groups based on their visit to the hospital for management of suicidal ideation or suicide attempt and other mental problems, respectively. Results There were differences in the year of visit, diagnosis, education level, and referral sources between patients in the suicidal and non-suicidal groups. Multiple regression analysis was conducted based on the sex, education level, referral by school, and diagnosis of depression in patients in the suicidal group, which revealed significant association. Conclusion Suicide-related problems were significantly associated with the sex, education level, referral by school, and a diagnosis of depression in the patients. A well-connected referral system would be necessary for professional mental health management of high-risk children and adolescents.

Babesiosis is a tick-transmitted intraerythrocytic zoonosis. In Korea, the first mortalities were reported in 2005 due to Babesia sp. detection in sheep; herein we report epidemiological and genetic characteristics of a second case of babesiosis. Microscopic analysis of patient blood revealed polymorphic merozoites. To detect Babesia spp., PCR was performed using Babesia specific primers for β-tubulin, 18S rDNA, COB, and COX3 gene fragments. 18S rDNA analysis for Babesia sp., showed 98% homology with ovine Babesia sp. and with Babesia infections in Korea in 2005. Moreover, phylogenetic analysis of 18S rDNA, COB, and COX3 revealed close associations with B. motasi. For identifying the infectious agent, Haemaphysalis longicornis (296) and Haemaphysalis flava (301) were collected around the previous residence of the babesiosis patient. Babesia genes were identified in three H. longicornis: one sample was identified as B. microti and two samples were 98% homologous to B. motasi. Our study is the first direct confirmation of the infectious agent for human babesiosis. This case most likely resulted from tick bites from ticks near the patient house of the babesiosis patient. H. longicornis has been implicated as a vector of B. microti and other Babesia sp. infections.

Background Cancer is a complex disease with profound genomic alterations and extensive heterogeneity. Recent studies on large-scale genomics have shed light on the impact of core oncogenic pathways, which are frequently dysregulated in a wide spectrum of cancer types. Aberrant activation of the hepatocyte growth factor (HGF) signaling axis has been associated with promoting various oncogenic programs during tumor initiation, progression, and treatment resistance. As a result, HGF-targeted therapy has emerged as an attractive therapeutic approach. However, recent clinical trials involving HGF-targeted therapies have demonstrated rather disappointing results. Thus, an alternative, in-depth assessment of new patient stratification is necessary to shift the current clinical course. Methods To address such challenges, we have evaluated the therapeutic efficacy of YYB-101, an HGF-neutralizing antibody, in a series of primary glioblastoma stem cells (GSCs) both in vitro and in vivo. Furthermore, we performed genome and transcriptome analysis to determine genetic and molecular traits that exhibit therapeutic susceptibility to HGF-mediated therapy. Results We have identified several differentially expressed genes, including MET, KDR, and SOX3, which are associated with tumor invasiveness, malignancy, and unfavorable prognosis in glioblastoma patients. We also demonstrated the HGF-MET signaling axis as a key molecular determinant in GSC invasion, and we discovered that a significant association in HGF expression existed between mesenchymal phenotype and immune cell recruitment. Conclusions Upregulation of MET and mesenchymal cellular state are essential in generating HGF-mediated therapeutic responses. Our results provide an important framework for evaluating HGF-targeted therapy in future clinical settings.

Current chemotherapy regimens have certain limitations in improving the survival rates of patients with advanced ovarian cancer. Hepatocyte growth factor (HGF) is important in ovarian cancer cell migration and invasion. This study assessed the effects of YYB-101, a humanized monoclonal anti-HGF antibody, on the growth and metastasis of ovarian cancer cells. YYB-101 suppressed the phosphorylation of the HGF receptor c-MET and inhibited the migration and invasion of SKOV3 and A2780 ovarian cancer cells. Moreover, the combination of YYB-101 and paclitaxel synergistically inhibited tumor growth in an in vivo ovarian cancer mouse xenograft model and significantly increased the overall survival (OS) rate compared with either paclitaxel or YYB-101 alone. Taken together, these findings suggest that YYB-101 has therapeutic potential in ovarian cancer when combined with conventional chemotherapy agents.

This study identifies the aspects of a managers` perceived work experience in a Multicultural Family Support Center and analyzes how work experience backgrounds are formulated. In-depth interviews were conducted with 10 managers from March to September 2015 to understand managers` work experience. Descriptions from the interviews were analyzed using phenomenological research methods. The result show that their work experience can be categorized into 73 meanings, 10 subcategories, and five themes. The five themes are `program development,` `employees assignment optimization,` `use and control network resources,` `deal with changes in needs of multicultural families,` and `supports vs. controls.` The analysis of the themes and subcategories from each theme allows us to first interpret that managers consider their significant and diversified work tasks overwhelming. Second, they find their jobs fit them and feel personally interested with a sense of duty from their work to overcome stress from heavy workloads. Third, managers put a high value on their work as a hands-on experience that is an officially authorized position from the government. Fourth, they are proud that they contribute to offering welfare services to multicultural families as members of Multicultural Family Support Centers.

The purpose of this study is to the motion expression activities of children with intellectual disabilities using motion graphics and Kinect. In the process of recognizing movement expression activity using motion graphics and Kinect, the effect of performance was shown when the movement expression activity through the body was properly performed. The subjects were 8 children with intellectual disabilities, and conducted the program twice a week for 10 weeks. The research design utilized video screen and theme music as contents of musical works. 42 actions were performed randomly. When the movement is perfectly represented, the score is displayed along with the sound. As a research method, Laban Movement analysis was used as a motion expression activity program. It is analyzed by four elements of LMA: Body, Effort, Shape, and Space. We observed the connectivity, body structure, body movements, progress, gestures and postures of each part of the body measured by LMA and figured out what the content of movement was. When the anatomical position of the body is divided into upper/lower (vertical) (average: 34/42: total score), left/right (horizontal) (average: 23/42: total score), and front/back (sagittal) (average: 13/42: total score). Through this study, it is shown that the movement of the children with intellectual disabilities can be induced by using the motion graphics and the functional game using Kinect to train the body structure and movement direction in daily life and to induce the change of the internal attitude.

Temozolomide (TMZ) is an alkylating agent used for the treatment of glioblastoma. The late autophagy inhibitor chloroquine (CQ) inhibits glioblastoma tumors in a p53-independent and p53-dependent manner. We addressed a possible beneficial effect of combination treatment with TMZ and CQ by examining the molecular and cellular mechanism of co-treatment. Combination treatment of U87 cell (wild type p53) with TMZ and CQ synergistically reduced cell proliferation and enhanced apoptosis, with increased sub-G 1 hypodiploid cells and caspase activation. This effect was abolished by a pan-caspase inhibitor, Z-VAD-FMK. TMZ induced autophagy, and the addition of CQ further increased autophagic vacuoles. Inhibition of early stages of autophagy by Beclin 1 knockdown and 3-methyladenine pretreatment prevented the enhanced effect of the combination treatment. The combination treatment also upregulated p53 and phospho-p53 levels, whereas p53 knockdown or overexpression of mutant p53 abolished the combination effect. In contrast, combination therapy had no enhanced effect on U373 cell (mutant p53) proliferation and apoptosis within 3 d, although TMZ induced autophagy and co-treatment with CQ increased autophagic vacuole accumulation. However, long term combination treatment for 9–10 d effectively decreased clonal and cellular growth with increased G 2 –M arrest. This effect was also abolished by Beclin 1 knockdown. Our data support the beneficial effect of combination treatment with TMZ and CQ in glioma via differential autophagy-associated mechanisms, depending on p53 status.

Background: YYB101, a humanized monoclonal antibody against hepatocyte growth factor (HGF), has shown safety and efficacy in vitro and in vivo. This is a first-in-human trial of this antibody. Materials and Methods: YYB101 was administered intravenously to refractory cancer patients once every 4 weeks for 1 month, and then once every 2 weeks until disease progression or intolerable toxicity, at doses of 0.3, 1, 3, 5, 10, 20, 30 mg/kg, according to a 3+3 dose escalation design. Maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamics were studied. HGF, MET, PD-L1, and ERK expression was evaluated for 9 of 17 patients of the expansion cohort (20 mg/kg). Results: In 39 patients enrolled, no dose-limiting toxicity was observed at 0.3 mg/kg, and the most commonly detected toxicity was generalized edema ( n = 7, 18.9%) followed by pruritis and nausea ( n = 5, 13.5%, each), fatigue, anemia, and decreased appetite ( n = 4, 10.8%, each). No patient discontinued treatment because of adverse events. YYB101 showed dose-proportional pharmacokinetics up to 30 mg/kg. Partial response in 1 (2.5%) and stable disease in 17 (43.5%) were observed. HGF, MET, PD-L1, and ERK proteins were not significant predictors for treatment response. However, serum HGF level was significantly lowered in responders upon drug administration. RNA sequencing revealed a mesenchymal signature in two long-term responders. Conclusion: YYB101 showed favorable safety and efficacy in patients with refractory solid tumors. Based on this phase I trial, a phase II study on the YYB101 + irinotecan combination in refractory metastatic colorectal cancer patients is planned. Conclusion: ClinicalTrials.gov Identifier: NCT02499224

Babesiosis is an emerging tick-borne disease in humans worldwide; however, little is known about the frequency of infection or prevalence of this disease in other parts of the world, excluding North America. In this study, we aimed to investigate Babesia microti infection frequency in a human population in Mongolia. One hundred blood samples were collected from stock farmers living in Khutul city of Selenge province, Mongolia. The sera and DNA from blood samples were evaluated for the presence of B. microti infection by using indirect fluorescent antibody (IFA) tests and PCR. The positive detection rates obtained using the IFA tests and PCR assays were 7% and 3%, respectively. This study is the first to detect of B. microti infections based on antibody seroprevalence or PCR assays for the presence of B. microti DNA in a Mongolian population.

DNA lesion-induced centrosomal abnormalities during the replication phase are relatively unknown. Here, we report that RNAi-mediated depletion of RRM1 induces cell-cycle arrest at the replication phase, along with severe DNA damage and centrosomal amplification. Interestingly, CHK1 depletion synergistically increased RRM1-depletion-induced centrosomal amplification. In response to hydroxyurea, CHK1 was delocalized from the centrosome by RRM1 depletion. Moreover, CDK1, which functions in centrosome separation and is inhibited by CHK1, was found to be essential for RRMI1-depletion-induced centrosomal amplification. Thus, we herein demonstrate that RRM1 preserves chromosomal stability via the CHK1- and CDK1-dependent stabilization of the centrosomal integrity at the replication stage.

Previous studies demonstrated that Clonochis sinensis-derived crude antigens suppress development of allergic responses. We investigated the effects of C. sinensis venom allergen-like (CsVAL) proteins on immune-modulating activities in allergic inflammatory response. Using RBL-2H3 rat mast cells, we demonstrated that CsVAL inhibits antigen-induced β-hexosaminidase release from immunoglobulin E-sensitized RBL-2H3 cells, and this inhibitory activity occurs by suppressing Lyn phosphorylation and intracellular reactive oxygen species production. In addition, CsVAL peptide treatment inhibits activation of protein kinase C-α and extracellular signal-regulated kinase 1/2, which are involved in degranulation of immunoglobulin E-sensitized mast cells. Furthermore, immunization with CsVAL suppressed development of skin inflammation by assessing ear thickness and cutaneous infiltration by eosinophils and mast cells in oxazolone-induced contact hypersensitivity in vivo mouse model. These results suggest that CsVAL is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases.

The synthetic machinery of ATF4 (activating transcription factor 4) is activated in response to various stress conditions involved in nutrient restriction, endoplasmic reticulum homeostasis, and oxidation. Stress-induced inhibition of proteasome activity triggers the unfolded protein response and endoplasmic reticulum stress, where ATF4 is crucial for consequent biological events. In the current study, we showed that the NAD(+)-dependent deacetylase, SIRT1, suppresses ATF4 synthesis during proteasome inhibition. SIRT1 depletion via transfection of specific siRNA into HeLa cells resulted in a significant increase in ATF4 protein, which was observed specifically in the presence of the proteasome inhibitor MG132. Consistent with SIRT1 depletion data, transient transfection of cells with SIRT1-overexpressing plasmid induced a decrease in the ATF4 protein level in the presence of MG132. Interestingly, however, ATF4 mRNA was not affected by SIRT1, even in the presence of MG132, indicating that SIRT1-induced suppression of ATF4 synthesis occurs under post-transcriptional control. Accordingly, we propose that SIRT1 serves as a negative regulator of ATF4 protein synthesis at the post-transcriptional level, which is observed during stress conditions, such as proteasome inhibition.

Purpose: To investigate the prevalence of Toxoplasma gondii and Toxocara canis in patients with uveitis.Methods: Patients with uveitis were examined. Serum antibodies to T. gondii and T. canis were tested by using the enzyme-linked immunosorbent assay. Polymerase chain reaction (PCR) was done using blood and aqueous humor (AH).Results: Ninety-eight patients were enrolled. Mean age was 43.5 ± 13.2 years. Six patients were seropositive for T. gondii with the following pattern: anterior uveitis, 1; posterior uveitis with retinitis, 2; pan uveitis, 2. One patient had a positive PCR result for T. gondii in AH, who showed panuveitis. Twenty-three patients were positive to serum IgG for T. canis with the following clinical manifestation: granuloma, 6; pigmented scar, 3; vitritis, 6—but none were PCR positive.Conclusions: T. gondii and T. canis are still important causes of uveitis. Ocular toxocariasis is not an uncommon cause of uveitis, even in adults.

Several epidemiological surveys have reported the prevalence of Toxoplasma gondii infection in stray cats in Korea, but little information is available on T. gondii infection in household cats. The aim of the present study was to assess the prevalence and risk factors of T. gondii infection among household cats reared in Seoul, Korea. A total of 474 blood samples were collected from clinically healthy household cats. All samples were tested using ELISA and PCR. The risk factor analysis was based on a questionnaire filled out by the owners. The overall positive rate for ELISA and PCR assays was 2.2% (10/437) and 2.1% (10/474), respectively. With regard to the origin of cats, the positive rates among cats adopted from the animal shelter and veterinary clinic for stray cats were significantly different (P

Bovine viral diarrhea virus (BVDV) is very important disease in domestic and wild ruminants and has a world wide distribution. Cattle persistently infected with BVDV (BVDV-PI) are the primary reservoir for BVDV infection in Korean native cattle herds. The prevalence of cattle persistently infected with BVDV (BVD-PI) was determined using 4,260 heads from 29 Korean native cattle farms at 8 districts from 2011 to 2012. The sera and ear nothches were collected for each sample. We surveyed BVD-PI cattle using antibody ELISA and antigen capture ELISA for detection of antibody and antigen respectively. Three thousand seventy-six cattle (72.2%) were positive for BVDV antibody and a total of 27 BVD-PI cattle were found in 12 farms. 11 cattle (40.7%) out of the total 27 BVDV-PI cattle were six months old or under. The positive rate of BVDV antibody (83.2%) from 12 farms with BVD-PI cattle was higher than the positive rate of BVDV antibody (63.6%) from 17 farms without BVD-PI cattle.

This study surveyed the Toxoplasma (T.) gondii infection prevalence in the Korean rabbit population. Rabbits (n=142) were obtained from two breeding farms in the Gongju area, Chungnam Province, and in the Kochang area, Junbuk Province, Korea. Of 142 sera samples analyzed by enzyme-linked immunosorbent assay (ELISA), 15 (10.6%) exhibited T. gondii-specific IgG antibodies, and 1 (0.7%) rabbit harbored T. gondii-specific IgM. Female rabbits (9/84; 10.7%) had a similar T. gondii prevalence to males (6/58; 10.3%). When stratified by age, rabbits aged >1 year had a similar prevalence of T. gondii infection (7/66; 10.6%) to rabbits aged 1 year had a similar prevalence (12/66; 18.2%) of T. gondii infection to rabbits aged

We assessed the prevalence of Enterobius vermicularis infection and changes in the egg positive rate (EPR) over 1-year time, using the adhesive cellophane-tape perianal swab method in 2,347 preschool children in Muan-gun, Jeollanam-do, Republic of Korea in 2008 and 2009. The overall EPR for E. vermicularis was 4.1% in 2008 and 4.5% in 2009. A study population of 389 children was repeatedly examined for 2 years. Within this group, the EPR in 2009 was twice higher than in 2008, and the EPR of the group of 5-7-year-old children was significantly higher than that of other age groups. Moreover, in the group of 5-7-year-old children in 2009, the rates of positive and negative conversion were significantly higher and lower, respectively, than in other age groups. Conclusively, enterobiasis was prevalent during 2008-2009 among preschool children in Muan-gun, Jeollanam-do, and the increased EPR in 2009 was due to an increase in newly acquired infections among 5-7-year-old children.